tbuckley/cabot-search huggingface dataset:
Abstract 9706: A Novel High Energy Phosphate Source Resuscitates Poorly Functioning Donor Hearts
Authors: Salwa A Elgebaly, Robert Poston, Charles Van Buren, Robert Todd, Reem Arafa, Nashwa El-Khazragy, Mostafa Rabie, Ahmed Mohamed, Lamiaa Ahmed, Nesrine El Sayed
Journal: Circulation (2022)

Introduction: Over 60% of the time donor hearts cannot be utilized for transplant, mostly because of poor left ventricular ejection fraction (EF) of ≤40% due to stress cardiomyopathy (i.e., demand ischemia) with depletion of myocardial adenosine triphosphate (ATP). The bioenergetic cyclocreatine phosphate (CCrP) is an FDA Orphan Designated Drug for heart transplantation . When CCrP is given prophylactically in an isoprenaline (ISO) rat model of demand ischemia, it restored ATP and maintained contractility. Hypothesis: We hypothesized that administering CCrP therapeutically after ISO-induced myocardial dysfunction in rats (simulating rejected donor hearts), will prevent ischemic injury and sustain long-term restoration of EF. Methods: Wistar male rats (180-220 g) were injected SC with ISO (85 and 170 mg/kg/day) for two consecutive days. CCrP (n=6, 0.8 gm/kg/day ip) and saline control (n=4) were administered 1 hour after completing the course of ISO injections and then daily for 2 weeks. A negative control group was injected with saline (n=4). Serum CK-MB and ECG/ST were measured 24 hours after last ISO injection. Evidence of stress cardiomyopathy was assessed after 14 days by ECHO analysis for EF and levels of hs-Troponin I (TnI) and BNP. One-way ANOVA analysis was used. Results: Table I shows two main benefits of therapeutically administered CCrP in this stress cardiomyopathy model: 1) poor heart function was quickly restored in the acute phase (24 hours), as indicated by normal ECG/ST and CK-MB levels; and 2) the restoration of function was sustained over the long term (14 days), as indicated by normal EF% and levels of hs-TnI and BNP. Conclusions: The bioenergetic CCrP is a novel cardioprotective drug that appears to salvage cardiac dysfunction and restore normal EF% in a rat model of stress cardiomyopathy. If this benefit translates into clinical organ donors with poor heart function, CCrP could be used to increase heart utilization for transplantation.
Abstract 9599: Impact of Sex on Outcomes After WATCHMAN FLX Implantation
Authors: Devi Nair, Jonathan P Piccini, Jonathan C Hsu, douglas gibson, James V Freeman, Robert W Yeh, Matthew J Price, Thomas Christen, Dominic Allocco, Samir R Kapadia
Journal: Circulation (2022)

Introduction: Female sex is an established, non-modifiable risk factor for adverse outcomes in atrial fibrillation (AF) patients. Left atrial appendage occlusion (LAAO) has been shown to be generally safe and effective for stroke prevention in patients with AF. Data on sex-based outcomes with WATCHMAN FLX is lacking. Methods: WATCHMAN FLX patients from the National Cardiovascular Data Registry LAAO Registry between August 5th 2020 and March 31st 2021 were analyzed. Results: Women at baseline had a higher average CHA 2 DS 2 -VASc score, were more likely to have a history of transient ischemic attack, thromboembolic event, peripheral or carotid artery disease, fall risk, and chronic lung disease than men. Conversely, history of congestive heart failure, left ventricular dysfunction, hypertension, diabetes, vascular disease, abnormal renal function, cardiomyopathy, non-paroxysmal atrial fibrillation, myocardial infarction, prior cardiac interventions, alcohol use, antiplatelet medication use and non-steroidal anti-inflammatory drug use were all reduced in women compared to men. The early safety endpoint was similar between women and men ( Table ). At 45 days, unadjusted rates of major adverse events were higher in women than men mainly due to differences in major bleeding and pericardial effusion ( Table ). The risk of death was lower in women than men at 45 days. Rates of stroke, major vascular complications, systemic thromboembolism, myocardial infarction, and device-related thrombus were not significantly different between sexes. Adjusted outcomes will be available at the time of the presentation. Conclusions: In this national unselected cohort, there are significant sex-based differences in baseline characteristics and comorbidity burden. Women experienced more major adverse events after LAAO than men. Additional research to determine the underlying mechanisms of the increased risk in women and strategies for closing the gap between sexes are needed.
Abstract 9608: Upregulation of Cardiac Beta3-Adrenergic Receptor-Activated iNOS Uncoupling Promotes Diabetic Cardiomyopathy in Type II Diabetic Mice: Role of Oxidant Stress
Authors: Heng-Jie Cheng, Jing Cao, Xiaoqiang Sun, David X Zhao, Dalane W Kitzman, Che Ping Cheng
Journal: Circulation (2022)

Background: Recent evidence highlights oxidative stress as an important mechanism to cardiac dysfunction in type 2 diabetes (T2D) and altered β 3 -adrenergic receptor (AR)-activated nitric oxide synthase (NOS) pathway contributing to this process. However, the NOS isoforms involved are controversial. The mechanism of how β 3 -AR stimulation impacts ROS, SERCA2a, and cardiac function in T2D is unclear. We tested the hypothesis that oxidant stress from upregulation of LV β 3 -AR-activated iNOS uncoupling promotes T2D cardiomyopathy. Methods: We compared myocyte β 1 - and β 3 -AR, NOS, peroxynitrite (NT), NADPH and SERCA2a expressions and myocyte functional responses to β- and β 3 -AR stimulation with isoproterenol (ISO,10 -8 M) and BRL-37344 (BRL,10 -8 M), respectively, in the absence and presence of iNOS inhibitor, 1400W (10 -5 M) of female mice over 14 weeks (W): 7 normal and 7 with T2D induced by 14 W high-fat diet (HFD) intake, but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. 5 days). Results: Versus normal myocytes, T2D myocytes had significantly increased protein levels of β 3 -AR (0.25 vs 0.14) and iNOS (0.25 vs 0.15) accompanied with increased oxidative stress indicated by significantly-elevated NT formation, NADPH (P67 -phox , 33% and p22 -phox , 29%) and decreased GTPCH expression (0.43 vs 0.85) and activity. T2D myocytes had significantly decreased β 1 -AR (0.35 vs 0.49) and SERCA2a (0.19 vs 0.29). These changes were associated with reduced cell contraction (dL/dt max , 75.4 vs 133.7 μm/s), relaxation (dR/dt max , 59.6 vs 113.8 μ m/s), and [Ca 2+ ] iT (0.16 vs 0.21) accompanied by diminished β-AR-stimulated positive inotropic response, but enhanced β 3 -AR-induced negative inotropic response. Only in T2D myocytes, pretreatment with 1400W improved basal cell function and augmented ISO-increased dL/dt max (64.5%) and [Ca 2+ ] iT (29.2%), but significantly limited BRL-induced decrease in dL/dt max (12.7%) and [Ca 2+ ] iT (9.8%). Conclusions: T2D is associated with contrasting changes on myocyte β 1 - and β 3 -AR expression with decreased SERCA2a and increased iNOS. Upregulation of β 3 -AR triggers iNOS uncoupling, leading to oxidative stress, thus promoting intrinsic myocyte dysfunction with impaired [Ca 2+ ] i regulation and reduced β-AR reserve.
Abstract 9795: The Association Between Albumin and Outcomes in Heart Failure and Secondary Mitral Regurgitation: Insights From the COAPT Trial
Authors: Kent Y Feng, Andrew P Ambrosy, Ditian Li, Jeremy Kong, Jonathan Zaroff, Jacob Mishell, Ivy A Ku, Andrea Scotti, Augustin Coisne, Bjorn Redfors, Michael Mack, William T Abraham, Joann Lindenfeld, Gregg Stone
Journal: Circulation (2022)

Background: Low serum albumin level is associated with increased morbidity and mortality in numerous chronic diseases, but the relationship between albumin and outcomes in heart failure (HF) and secondary mitral regurgitation (SMR) has not been previously described. Methods: The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial was a multicenter, randomized, controlled, parallel-group, open-label study that evaluated the efficacy and safety of transcatheter edge-to-edge repair (TEER) with the MitraClip + guideline-directed medical therapy (GDMT) versus GDMT alone in patients with symptomatic HF and moderate-to-severe or severe SMR. Baseline serum albumin level was obtained at enrollment. Results: Among 614 patients enrolled in COAPT, 559 (91.0%) had a baseline albumin level (median 4.0 g/dL [interquartile range: 3.7-4.2 g/dL]). Patients with albumin &lt;4.0 g/dL compared with ≥4.0 g/dL were older (mean 73.7 years vs. 70.6), more likely to have ischemic cardiomyopathy (65.0% vs. 555.2%) and a hospitalization within the prior year (72.9% vs. 62.9%). After multivariable adjustment, patients with albumin &lt;4.0 g/dL compared to ≥4.0 g/dL had higher 2-year rates of all-cause mortality (41.7% vs. 28.8%; HR 1.46, 95% CI 1.06-2.02; p=0.022; Figure Panel A), but no significant differences in the composite of all-cause mortality or hospitalization for HF (HHF), HHF alone, or all-cause hospitalizations (all p&gt;0.05; Figure Panel B). There were no significant interactions between albumin and the relative efficacy of TEER + GDMT versus GDMT alone with respect to clinical outcomes (all p-interactions &gt;0.05; Figure Panel B). Conclusions: In patients with HF and severe SMR enrolled in the COAPT trial, low serum albumin levels were common and were an independent predictor of mortality. MitraClip treatment provided a similar benefit regardless of baseline albumin level.
Abstract 9806: Financial Strain and Ideal Cardiovascular Health: The Multi-Ethnic Study of Atherosclerosis
Authors: Olatokunbo Osibogun, Oluseye Ogunmoroti, Ruth-Alma N Turkson-Ocran, Victor Okunrintemi, Kiarri N Kershaw, Norrina B Allen, Erin D Michos
Journal: Circulation (2022)

Background: Psychosocial stress is associated with an increased risk of cardiovascular disease (CVD). The relationship between financial strain, a toxic form of psychosocial stress, and ideal cardiovascular health (CVH) is not well established. This study examined whether financial strain was associated with poorer CVH in a multi-ethnic cohort free of CVD at baseline. Methods: This is a cross-sectional analysis of 6,468 men and women aged 45-84 years. Two measures of financial strain were assessed: ongoing financial strain and ongoing financial strain for &gt;6 months. Responses to both measures were categorized as yes or no. CVH was measured from 7 metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure, and blood glucose). A CVH score was calculated from points assigned to the categories of each metric (poor = 0 points; intermediate = 1 point; ideal = 2 points) for a total of 14 points. Multinomial logistic regression was used to examine the association of financial strain with the CVH score (inadequate 0-8, average 9-10, and optimal 11-14 points) and number of ideal metrics, adjusting for sociodemographic factors. Results: The mean age (SD) was 62 (10) and 53% were women. Ongoing financial strain was reported by 25% of participants while 23% reported ongoing financial strain for &gt; 6 months. Participants who reported ongoing financial strain had lower odds of having average (0.82 [0.71, 0.94]) and optimal (0.73 [0.62, 0.87]) CVH scores ( Table ). Likewise, ongoing financial strain for &gt;6 months was associated with lower odds of having average (0.81 [0.70, 0.93]) and optimal (0.70 [0.58, 0.83]) CVH scores. Similar results were observed for the association of financial strain with the number of ideal metrics. Conclusions: Financial strain was associated with poorer CVH. More research is needed to understand this relationship so the burden of CVD can be decreased, particularly among people experiencing financial hardship.
Abstract 9230: Intraoperative Residual Lesion Score Predicts Major Residua at Discharge and Early Unplanned Reinterventions Following Congenital Heart Surgery
Authors: Aditya Sengupta, Kimberlee Gauvreau, Katherine Kohlsaat, Steven Colan, Jane W Newburger, Pedro J Del Nido, Meena Nathan
Journal: Circulation (2022)

Introduction: The Residual Lesion Score (RLS) has recently been validated as an important predictor of outcomes following congenital heart surgery. However, its reliance on the pre-discharge echocardiogram limits its utility. We assessed the intraoperative RLS (IO-RLS) as a predictor of outcomes following congenital cardiac surgery. Hypothesis: We hypothesized that IO-RLS would be an independent predictor of outcomes following congenital heart surgery. Methods: This was a single center, retrospective review of consecutive patients who underwent congenital cardiac surgery from 01/2011-12/2019. For each index operation, IO-RLS was assigned per the intraoperative echocardiogram using previously published criteria: Class 1, no residua; Class 2, minor residua; Class 3, major residua. Outcomes included major pre-discharge residua or in-hospital unplanned reintervention (primary) and unplanned reinterventions at 1-year post-surgery (secondary). Associations were evaluated using multivariable logistic regression, adjusting for age, prematurity, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) mortality category, and case complexity. Results: Of 6786 patients, 4743 (69.9%), 1903 (28.0%), and 140 (2.1%) patients had Class 1, 2, and 3 lesions, respectively. The primary outcome was observed in 988 (14.6%) patients. Both Class 2 and 3 patients had greater risk of the primary outcome ( Figure 1A ), compared to Class 1 patients. The predicted probability of major pre-discharge residua or in-hospital reintervention by STAT score and IO-RLS is shown in Figure 1B . At 1-year follow-up, 924 (13.6%) patients required reinterventions. IO-RLS Class 2 (OR 1.3, 95% CI 1.1-1.5, p=0.002) and Class 3 (OR 2.4, 95% CI 1.6-3.7, p&lt;0.001) patients had greater risk of the secondary outcome, versus Class 1 patients. Conclusions: IO-RLS may be an important adjunct for self-assessment and quality improvement in congenital heart surgery.
Abstract 9504: Endothelial Shear Stress Metrics Correlate With Inflammatory Markers at the Culprit Site of Erosion in Patients With an Acute Coronary Syndrome: An OPTICO-ACS Substudy
Authors: Mona Ahmed, David M Leistner, Diaa Hakim, Youssef Abdelwahed, Ahmet U Coskun, Charles Maynard, Claudio Seppelt, Nicholas Cefalo, Peter Libby, Ulf Landmesser, Peter H Stone
Journal: Circulation (2022)

Introduction: The pathobiological mechanisms of coronary plaque erosion are unclear. Low endothelial shear stress (ESS) is a proinflammatory/proatherogenic stimulus associated with coronary plaque progression/destabilization. Intravascular imaging studies suggest that high ESS gradient (low ESS areas adjacent to high ESS areas), and steepness of plaque upslope/downslope correlate with plaque erosion. We investigated the relationship of local fluid hemodynamics to the inflammatory microenvironment at the culprit site of erosion in patients with an acute coronary syndrome. Hypothesis: ESS metrics associate with proinflammatory/proatherogenic cells and cytokines, and contribute to plaque erosion. Methods: We studied 30 patients with erosion from the OPTIcal-COherence Tomography in Acute Coronary Syndrome study (OPTICO-ACS). OCT images were segmented, co-registered with the angiogram to create a 3D-reconstruction of the coronary artery. ESS metrics were calculated by Computational Fluid Dynamics. Systemic and local blood samples and thrombectomy specimens were collected at the culprit lesion and analyzed by flow cytometry-based immunophenotyping and plasma cytokine and chemokine profiling, and statistically tested for correlations of continuous variables using Spearman rank correlation (r). Results: Proinflammatory cytokines (IL6, MIP-1, IL1β, IL2) and local concentration of T-cells, including subsets of T-cells (CD4+, CD8+, and NKT-cells), were significantly higher at the culprit site of erosion and correlate with local adverse ESS metrics (Min ESS, Max ESS, Plaque Topographical Slope) (Table). Conclusion: Biomechanical features likely trigger activation of the adaptive immune system, including T-lymphocytes and their cytotoxic effector molecules. These results provide novel insights into the links between fluid hemodynamics, inflammatory activation, and mechanisms involved in the pathogenesis of coronary plaque erosion.
Abstract 280: Extracorporeal Cardiopulmonary Resuscitation Outcomes In Children Without Underlying Cardiac Disease
Authors: Morgann Loaec, Adam S Himebauch, Ron Reeder, Jessica Alvey, Jonathan Race, Lillian Su, Javier J Lasa, Julia C Slovis, Tia Raymond, Ryan Coleman, Todd J Kilbaugh, Alexis A Topjian, Robert M Sutton, Ryan W Morgan
Journal: Circulation (2022)

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) has been associated with improved outcomes compared to conventional CPR (CCPR) in children with underlying cardiac disease. There are limited data on ECPR survival outcomes in the non-cardiac population. Hypothesis: ECPR will be associated with improved survival to discharge in children without underlying cardiac disease with prolonged CPR. Methods: Retrospective cohort study using the AHA Get With The Guidelines® - Resuscitation registry of children (&lt;18 years) without cardiac disease who received ≥30 minutes of CPR for in-hospital cardiac arrest between 2000-2020. Weighted propensity scores were used to balance ECPR and CCPR groups based on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model was used to estimate the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR relative to the index year of 2000. Results: Of 875 patients, 159 received ECPR and 716 received CCPR (median age 1 year, primary diagnosis respiratory insufficiency, median CPR duration 45 minutes for full cohort). Survival to discharge was similar between the ECPR group (21.4%) compared to the CCPR group (16.2%) in both the univariable analysis (p= 0.13) and the propensity-weighted multivariable logistic regression (aOR 1.44 [CI 0.85-2.44, p= 0.173]. The Bayesian model estimated an 85.1% probability of a positive effect of ECPR on survival to discharge. ECPR use increased over time (test for trend p&lt;0.001). Conclusion: In children without cardiac disease who required ≥30 minutes of CPR, ECPR usage significantly increased in the last 20 years. Compared to CCPR, ECPR was not associated with a statistically significant increase in survival to discharge. However, a Bayesian model estimated weak evidence of a positive survival effect of ECPR.
Abstract 9318: The Safety, Pharmacokinetics, Pharmacodynamics and Immunogenicity of Ebronucimab in Healthy Volunteers: Result From a Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Dose-Escalation Study
Authors: Rui Chen, Zhuang Tian, Xiange Tang, Pei Hu, Lvya Wang, Yu Xia, Baiyong Li, Max Wang, Xiang Ni, Guoqin Wang, Shuyang Zhang
Journal: Circulation (2022)

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated to be effective therapeutic agents for lowing low-density lipoprotein cholesterol (LDL-C). Ebronucimab (AK102) is a novel fully human immunoglobulin G1 (IgG1) monoclonal antibody against PCSK9. The objective of this study is to investigate the safety and tolerability of ebronucimab in healthy subjects. Methods: A total of 32 healthy adult subjects were planned to be enrolled and treated in a dose escalation manner. In each cohort, 8 subjects were randomized in a 3:1 ratio to receive a single dose of ebronucimab (75, 150, 300 or 500 mg) or matching placebo via subcutaneous injection (Figure 1). Blood was drawn at pre-selected timepoints to evaluate the pharmacokinetic parameters, free PCSK9 concentration and anti-drug antibody (ADA). Safety assessment was carried out up to day 85 ± 3 or early termination visit. Results: Safety Among the 32 subjects recruited, 87.5% (21/24) subjects administrated ebronucimab and 75% (6/8) subjects treated with placebo reported treatment emergent adverse events (TEAEs). The majority of adverse events were mild and moderate in severity. No relationship was identified between the dose of ebronucimab and the incidence of TEAEs. No TEAEs leading to study discontinuation and death were reported. Pharmacokinetics (PK)/Pharmacodynamics (PD) Following a single subcutaneous injection of 75 mg to 500 mg ebronucimab in healthy subjects, the median of T max ranged from 2.0 to 6.0 days and t 1/2 was within 4.11 to 5.01 days across cohorts. C max, AUC 0-t , and AUC 0-∞ increased approximately in a dose-proportional manner, see Table 1 and Figure 2. Serum free PCSK9 was almost completely inhibited after ebronucimab injection. The lowest level of free PCSK9 was observed around 2 days post administration and maintained at a low level 14-22 days post injection, see Figure 3. Immunogenicity A total of 3 subjects were tested ADA positive at least once during the study (75 mg, 1 subject; 500 mg, 2 subjects). The incidence of ADAs in subjects treated with ebronucimab was 12.5 % (3/24). Conclusions: Ebronucimab was well tolerated in healthy subjects and no special safety signal was identified during the study.
Abstract 9811: A Novel Analysis of Patient, Provider, and Utilization Factors Associated With an Electronic Health Record (EHR)-Embedded Guideline-Directed Medical Therapy Score
Authors: Trejeeve Martyn, Joshua Saef, Umesh N Khot, Todd Brophy, Kathryn A Martinez, Lucianne West, Cristiani Cari, Hunter Block-Beach, Jessica Hohman, Samir R Kapadia, Wai Hong W Tang, Christopher Babiuch, Jerry Estep, Randall Starling
Journal: Circulation (2022)

Introduction: Health systems have had limited success in improving on the suboptimal use of medical therapy for heart failure (HF). Hypothesis: We sought to understand if Guideline-Directed Medical Therapy (GDMT) scoring in combination with EHR-based HF registry data could be utilized to delineate system factors associated with higher or lower GDMT scores. Methods: We performed a cross-sectional analysis of patients with ≥ 2 outpatient encounter for heart failure (HF) in the prior 24 months. Total GDMT score was based on the absence, presence, and dosage of pertinent medications (Fig.1). Multivariable logistic regression analysis of patient, provider, and acute utilization factors associated with GDMT score above the median was performed. Results: Among 6,454 HF patients who had a documented echocardiographic LVEF ≤40 in in the prior 24 months, we observed that having a GDMT score ≥ 4 was associated with having a HF physician encounter (OR:2.02, 95%CI: 1.77-2.32), having two cardiology visits (any sub-specialty) within the prior 12 months (OR: 1.44,95%CI: 1.26-1.65), fewer all-cause (OR: 0.91, 95%CI: 0.87-0.94) and HF-specific hospitalizations (OR:0.64, 95%CI: 0.53-0.75), and higher eGFR (OR: 1.18, 95%CI: 1.12-1.25) (Fig. 2). Conclusions: GDMT scoring that is embedded in an EHR-Based Heart Failure Registry can help to define system-specific system factors associated with, the use of optimal HF medical therapy. Connectivity to cardiology, particularly HF specialists, was independently associated with higher GDMT score in our health system.